Detection Of Liver And Renal Function Abnormalities In The Australian & New Zealand Population Of Fontan Patients
Funder
National Health and Medical Research Council
Funding Amount
$345,080.00
Summary
Children born with complex heart defects and only one pumping chamber can now live into adulthood with an operation called the Fontan procedure. As this operation has only existed for 40 years, the long-term expectations for these children and young adults are still unclear, and their population is growing every year. There is now evidence that they may suffer from liver and kidney failure. This project will identify the severity of liver and kidney damage in our population of Fontan patients.
Unraveling Mechanisms Of Liver Transplant Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$694,822.00
Summary
Liver transplants are unique amongst solid organs as they are spontaneously accepted across different individuals and induce acceptance of other organs from the same donor co-transplanted at the same time. Using a new mouse liver transplantation model, this proposal will elucidate how the liver tissue performs this function and identify new markers associated with tolerance in the blood of mice. This knowledge will be used to identify liver transplant patients with reduced rejection risk.
Preconditioning: The Molecular Basis For Protection From Hepatic Ischemia-reperfusion Injury
Funder
National Health and Medical Research Council
Funding Amount
$406,980.00
Summary
When the blood supply to the liver is cut off temporarily (ischemia) and later restored (reperfusion) the liver is damaged by a process called ischemia-reperfusion (IR) injury. This is a major problem during liver surgery and is also an underlying problem in liver transplantation; following storage of a donor liver ready for placing into the recipient it can undergo a similar process called preservation injury. We now understand a lot about how IR comes about, particularly by the formation of da ....When the blood supply to the liver is cut off temporarily (ischemia) and later restored (reperfusion) the liver is damaged by a process called ischemia-reperfusion (IR) injury. This is a major problem during liver surgery and is also an underlying problem in liver transplantation; following storage of a donor liver ready for placing into the recipient it can undergo a similar process called preservation injury. We now understand a lot about how IR comes about, particularly by the formation of damaging oxygen radicals within liver cells to start a process of programmed cell death, but it remains difficult to prevent or treat IR injury. A recent breakthrough has been recognition that subjecting the liver to only a short period (5 or 10 minutes) of ischemia protects against a later period of prolonged ischemia or IR. In the investigator s mouse model, for example, such preconditioning was 60 to 90% protective (depending on the time after IR). This project seeks to understand how preconditioning works to protect the liver against IR injury. Our idea is that preconditioning generates a limited amount of oxygen radicals, and that these turn on signalling pathways in the cell that regulate certain protective genes. Genes that encode antioxidant and other anti-stress pathways are likely to be important, but so are genes that prepare the cell to enter the cell cycle and divide into new cells that regenerate the liver. Conversely, genes that program cell death may be turned off. The outcomes of this research will be to understand the molecular and cellular basis of how preconditioning protects against ischemia-reperfusion injury of the liver. This will allow drug treatments to be devised that, by simulating preconditioning, prevent this common and severe type of liver damage.Read moreRead less
Pathophysiology And Treatment Of Nonalcoholic Fatty Liver Disease: Effects Of Bariatric Surgery
Funder
National Health and Medical Research Council
Funding Amount
$88,766.00
Summary
The incidence of nonalcoholic fatty liver disease (NAFLD) is rising in parallel with the unfolding obesity crisis, and it will become the most common cause of liver failure in the near future. Bariatric surgery has established benefits in weight loss and type II diabetes remission. Its role in NAFLD is still uncertain. We will explore the role of bariatric surgery in the treatment of NAFLD, as well as investigate cellular and biomolecular changes that occur with weight loss.